American Association for Cancer Research

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Supplementary Tables from Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer

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posted on 2023-04-04, 00:46 authored by Nadia Tosti, Eleonora Cremonesi, Valeria Governa, Camilla Basso, Venkatesh Kancherla, Mairene Coto-Llerena, Francesca Amicarella, Benjamin Weixler, Silvio Däster, Giuseppe Sconocchia, Pietro Edoardo Majno, Dimitri Christoforidis, Luigi Tornillo, Luigi Terracciano, Charlotte K.Y. Ng, Salvatore Piscuoglio, Markus von Flüe, Giulio Spagnoli, Serenella Eppenberger-Castori, Giandomenica Iezzi, Raoul Andre Droeser

Supplementary Tables 1-5


Swiss Cancer League

Swiss National Science Foundation

Italian Association for Cancer Research



Immune cell infiltration in colorectal cancer effectively predicts clinical outcome. IL22, produced by immune cells, plays an important role in inflammatory bowel disease, but its relevance in colorectal cancer remains unclear. Here, we addressed the prognostic significance of IL22+ cell infiltration in colorectal cancer and its effects on the composition of tumor microenvironment. Tissue microarrays (TMA) were stained with an IL22-specific mAb, and positive immune cells were counted by expert pathologists. Results were correlated with clinicopathologic data and overall survival (OS). Phenotypes of IL22-producing cells were assessed by flow cytometry on cell suspensions from digested specimens. Chemokine production was evaluated in vitro upon colorectal cancer cell exposure to IL22, and culture supernatants were used to assess neutrophil migration in vitro. Evaluation of a testing (n = 425) and a validation TMA (n = 89) revealed that high numbers of IL22 tumor-infiltrating immune cells were associated with improved OS in colorectal cancer. Ex vivo analysis indicated that IL22 was produced by CD4+ and CD8+ polyfunctional T cells, which also produced IL17 and IFNγ. Exposure of colorectal cancer cells to IL22 promoted the release of the neutrophil-recruiting chemokines CXCL1, CXCL2, and CXCL3 and enhanced neutrophil migration in vitro. Combined survival analysis revealed that the favorable prognostic significance of IL22 in colorectal cancer relied on the presence of neutrophils and was enhanced by T-cell infiltration. Altogether, colorectal cancer–infiltrating IL22-producing T cells promoted a favorable clinical outcome by recruiting beneficial neutrophils capable of enhancing T-cell responses.

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